Safety evaluation of intravitreal use of a beta2‐agonist in rabbit eyes

Abstract

Abstract Purpose There is no known information on the use and safety of a long‐acting beta‐agonist, such as Clenbuterol when administered by intravitreal injection. Therefore, it is appropriate to perform this intravitreal injection in an animal model prior to start with a human experiment. The aim is to investigate the safety of an intravitreal injection of the beta2‐agonist Clenbuterol in rabbit eyes. This study is in preparation of using of this molecule in human eyes. That trial will be a monocentric, academic (investigator driven) trial to investigate the safety and efficacy of an intravitreal beta2‐agonist in patients with persistent subfoveal fluid after retinal detachment surgery. Approval of the ethics committee for the human trial has already been obtained, pending a re‐evaluation after the results of the animal study will be known. Methods An intravitreal injection of 0,1 ml solution containing 0.08µg Clenbuterol or 0.1ml NaCl 0.9% was given in 10 eyes of 10 rabbits. The distribution occurred at random and was masked. A masked investigator examined both eyes after 1, 3 and 7 days (biomicroscopy, intraocular pression and ophthalmoscopy). After one week, the rabbits were sacrificed, the eyes enucleated and fixated for histopathological examination and electron microscopy by a masked investigator. Cell death was monitored by a DNase type I/II activity assay. Results There was no clinical or histopathological difference between the clenbuterol and the control group. Conclusion Clenbuterol is not toxic for the retina of rabbit eyes after intravitreal injection. It can be considered for the use in human eyes. Final approval of the ethics committee for the human trial is awaited.